NICE cost-effectiveness appraisal of cholinesterase inhibitors: was the right question posed? Were the best tools used?

The National Institute for Health and Clinical Excellence (NICE) recently issued updated guidance on the use of cholinesterase inhibitors in the treatment of Alzheimer's disease. NICE initially recommended that cholinesterase inhibitors no longer be used, but final guidance restricted treatment to patients with disease of a moderately severe stage. This decision was based largely on results from a heavily criticised economic evaluation that used an adaptation of the Assessment of Health Economics in Alzheimer's Disease (AHEAD) model. As the developers of the AHEAD model, we examined the appropriateness of NICE's economic analyses and presentation of results. We attempted to replicate NICE's results by modifying the original AHEAD model. Sensitivity analyses were then run using the modified AHEAD model to evaluate the extent of uncertainty in predictions. The AHEAD(NICE) analyses resulted in an incremental cost-effectiveness ratio for galantamine of 82,000 pound per QALY gained (year 2003 values) from the perspective of the UK NHS and Personal Social Services. This was later revised to 46,000 pound per QALY, compared with < 9000 pound per discounted QALY gained (year 2001 values) in the original AHEAD model. Using our modified AHEAD with effectiveness estimates matching those of AHEAD(NICE), we show that NICE's choice and presentation of sensitivity analyses obscured the instability of their estimates. In the final NICE evaluation, the recommendation to delay treatment with cholinesterase inhibitors until patients have moderately severe disease was based on critical assumptions in the economic analyses that had little evidence to support them. The case of NICE's guidance on cholinesterase inhibitors highlights the importance of transparent and valid economic evaluations and the dangers of using inappropriate modelling technologies, basing analyses on a limited subset of the available data, and insufficiently reflecting the uncertainty in estimates that are intended to inform decision makers.     

Estimating 'costs' for cost-effectiveness analysis

Since 1999, the National Institute for Health and Clinical Excellence (NICE) Technology Appraisal Programme has been charged with producing guidance for the NHS in England and Wales on the appropriate use of new and existing healthcare programmes. Guidance is based on an assessment of a number of factors, including cost effectiveness. The identification, measurement and valuation of costs are important components of any cost-effectiveness analysis. However, working through these steps raises a number of important methodological questions. For example, how should 'future' resource use be estimated, and is there a need to consider all 'future' costs? Given that NICE produces national guidance, should national unit cost data be used to value resources or should local variations in negotiated prices be taken into account? This paper was initially prepared as a briefing paper as part of the process of updating NICE's 2004 Guide to the Methods of Technology Appraisal for a workshop on 'costs'. It outlines the issues that were raised in the original briefing paper and the subsequent questions that were discussed at the workshop.     

A stated preference binary choice experiment to explore NICE decision making

OBJECTIVE: To explore whether the National Institute for Health and Clinical Excellence (NICE) takes account of concerns other than just incremental cost effectiveness in commissioning healthcare services. METHOD: A stated preference binary choice experiment was used to explore the preferences of members of NICE's Appraisal Committees for incremental cost effectiveness, the degree of uncertainty surrounding incremental costs and health outcomes, the age of beneficiaries, baseline health-related quality of life (HR-QOL) and the availability of alternative therapies when considering whether to recommend health technologies. RESULTS: A logit modelling analysis of Committee members' stated preferences suggested that increases in the incremental cost-effectiveness ratio and economic uncertainty, and the availability of other therapies was associated with statistically significant reductions in the odds of a positive recommendation (p < 0.01). The transition from a very low to a comparatively high level of baseline HR-QOL was also associated with a statistically significant reduction in the odds of a positive recommendation (p = 0.003). The age of beneficiaries did not significantly affect decisions concerning whether to recommend technologies. CONCLUSION: The results of the choice experiment support the notion of a probabilistic adoption/rejection approach rather than the operation of a single cost-effectiveness threshold.     

Subgroups and heterogeneity in cost-effectiveness analysis

The National Institute for Health and Clinical Excellence (NICE) is required to consider cost effectiveness when issuing guidance about the use of health technologies within the UK NHS. Cost effectiveness is a means of supporting a system objective of maximizing population health gain from the available budget.There is a range of sources of variation between individuals in disease prognosis, and in the costs and effects of health technologies. It is often possible to explain some of this variation on the basis of the clinical and sociodemographic characteristics of patients. This facilitates subgroup-specific estimates of parameters in decision analytic models and provides a means of assessing heterogeneity in cost effectiveness between different types of patient. Given the objective of the NHS, there is a clear need for NICE, and similar decision makers in other systems, to reflect this heterogeneity by being as specific as possible about the characteristics of the recipients of new treatments.The use of subgroup analysis in cost-effectiveness analysis raises a number of methodological questions that have been given little consideration in the literature. They include a need to define the possible sources of heterogeneity that exist, which extends beyond relative treatment effect (which is the focus of clinical trial analysis) to include, for example, sources relating to baseline event rates. There is also the issue of how heterogeneity in model parameters should be estimated and how uncertainty should be appropriately quantified. A major issue also exists concerning the appropriateness, in terms of equity, of using all or some of the subgroup analyses as a basis of decision making. NICE needed to consider these and other issues when updating its methods guidance.     

NICE methodological guidelines and decision making in the National Health Service in England and Wales

The National Institute for Clinical Excellence (NICE) responds to requests by the Department of Health for guidance on the use of selected new and established technologies in the National Health Service (NHS) in England and Wales. This paper asks whether the NICE methodological guidelines help NHS decision makers meet the objectives of maximum health improvements from NHS resources and an equitable availability of technologies. The analytical basis of the guidelines is a comparison of the costs and consequences of new and existing methods of dealing with particular conditions using the incremental cost-effectiveness ratio. We explain why information on the costs and consequences of a particular technology in isolation is insufficient to address issues of efficiency of resource use. We argue that to increase efficiency, decision makers need information on opportunity costs. We show that in the absence of such information decision makers cannot identify the efficient use of resources. Finally we argue that economics provides valid methods for identifying the maximisation of health improvements for a given allocation of resources and we describe an alternative practical approach to this problem. Drawing on the experience of Ontario, Canada where an approach similar to that proposed by NICE has been in use for almost a decade, and recent reports about the consequences of NICE decisions to date, we conclude that instead of increasing the efficiency or equity of the use of NHS resources, NICE methodological guidelines may lead to: uncontrolled increases in NHS expenditures without evidence of any increase in total health improvements; increased inequities in the availability of services; and concerns about the sustainability of public funding for new technologies.     

Economic evaluation and decision making in the UK

This article reviews the development of economic evaluation of health technologies in the UK and its impact on decision making. After a long period of limited impact from studies mainly carried out as academic exercises, the advent of the National Institute for Health and Clinical Excellence (NICE) in 1999 provided a transparent decision-making context where economic evaluation plays a central role. This article reviews some of the key characteristics about the way NICE works, for example, the way NICE has defined the form of analysis that it requires, reflecting its objective of maximising health gain (QALYs) from the predetermined and limited UK NHS budget. Two broad areas of widespread concern are noted. The first relates to the cost-effectiveness thresholds that NICE uses and the basis for them. The second is the patchy implementation of NICE guidance and the possible reasons for this. But even within the UK, NICE is the exception in making extensive and explicit use of economic evaluation and this article goes on to suggest that if there is to be a more widespread and consistent use of economic evaluation at both central and local levels, then health economists and others need to address three issues. The first is to be clear about what is the correct conceptual basis for determining the cost-effectiveness threshold and then to ensure that NICE has the empirical evidence to set it appropriately. The second is to recognise that even using the limited view of costs adopted by NICE, economic evaluations imply temporal and cross-service budgetary flexibility that the NHS locally does not in practice enjoy. The third issue is that with academic pressures for ever-increasing sophistication of 'state of the art' economic evaluation analysis, the NHS has more and more precise understanding of the cost effectiveness of just a few new technologies and little or no analysis of most. This limits the value of the former by reducing further the scope for appropriately disinvesting from cost-ineffective technologies to meet the additional costs of investing in cost-effective new ones. Whilst NICE stands out as an example of a context where high-quality economic evaluation plays a major role in decision making, the process is far from perfect and certainly is not representative of the use made of economic evaluation by the NHS as a whole. Health economists need to engage with the public and the health service to better understand their perspectives, rather than focusing on academic concerns relating to details of theory and analytical method.     

Cost effectiveness of imatinib compared with interferon-alpha or hydroxycarbamide for first-line treatment of chronic myeloid leukaemia

OBJECTIVE: To evaluate the cost utility of imatinib compared with interferon (IFN)-alpha or hydroxycarbamide (hydroxyurea) for first-line treatment of chronic myeloid leukaemia. DESIGN AND SETTING: A cost-utility (Markov) model within the setting of the UK NHS and viewed from a health system perspective was adopted. Transition probabilities and relative risks were estimated from published literature. Costs of drug treatment, outpatient care, bone marrow biopsies, radiography, blood transfusions and inpatient care were obtained from the British National Formulary and local hospital databases. Costs (pound, year 2001-03 values) were discounted at 6%. Quality-of-life (QOL) data were obtained from the published literature and discounted at 1.5%. The main outcome measure was cost per QALY gained. Extensive one-way sensitivity analyses were performed along with probabilistic (stochastic) analysis. RESULTS: The incremental cost-effectiveness ratio (ICER) of imatinib, compared with IFNalpha, was pound26,180 per QALY gained (one-way sensitivity analyses ranged from pound19,449 to pound51,870) and compared with hydroxycarbamide was pound86,934 per QALY (one-way sensitivity analyses ranged from pound69,701 to pound147,095) [ pound1=$US1.691=euro1.535 as at 31 December 2002].Based on the probabilistic sensitivity analysis, 50% of the ICERs for imatinib, compared with IFNalpha, fell below a threshold of approximately pound31,000 per QALY gained. Fifty percent of ICERs for imatinib, compared with hydroxycarbamide, fell below approximately pound95,000 per QALY gained. CONCLUSIONS: This model suggests, given its underlying data and assumptions, that imatinib may be moderately cost effective when compared with IFNalpha but considerably less cost effective when compared with hydroxycarbamide. There are, however, many uncertainties due to the lack of long-term data.     

Cost-effectiveness analyses of natalizumab (Tysabri) compared with other disease-modifying therapies for people with highly active relapsing-remitting multiple sclerosis in the UK

BACKGROUND: Natalizumab (Tysabri) is a new disease-modifying therapy that has been shown to be clinically effective in patients with relapsing-remitting multiple sclerosis (RRMS) and has been licensed for use in patients with highly active RRMS (HARRMS). These patients are those who experience higher relapse rates and faster disability progression than the general RRMS population. OBJECTIVES: To estimate the cost effectiveness of natalizumab compared with interferon-beta, glatiramer acetate and best supportive care from various UK cost perspectives. METHODS: A 30-year Markov model was developed, based on previously published models for multiple sclerosis, to estimate transition between disability states and the probability of relapse within disability states. The model was parameterized with data from the UK Multiple Sclerosis (MS) Survey 2005 and data from the AFFIRM study, a 2-year multicentre, randomized, double-blind, placebo-controlled trial of natalizumab in RRMS patients. Additional data were sourced from the literature. A UK societal cost perspective was used in the base case, with additional cost perspectives considered in the sensitivity analysis. The baseline characteristics for the patient group were taken from the patient population in the AFFIRM study (mean age 36 years, mean time since diagnosis 5 years and a mean Kurtzke Extended Disability Status Scale [EDSS] score of 2.5). The model and its parameterization were designed and developed to support a reimbursement application for natalizumab submitted to the UK National Institute for Health and Clinical Excellence (NICE). Efficacies for natalizumab and glatiramer acetate were taken from clinical trial data, and for interferon-beta from a meta-analysis of clinical trial data. Disutilities from adverse events for each comparator were also included in the model. Outcomes and costs were discounted at 3.5% per anum.Costs for interferon-beta and glatiramer acetate were based on published prices (year 2006 values) under the UK Risk Sharing Scheme, and for natalizumab the UK NHS list price was used. Diagnostic, administration and adverse event costs were also included. The incremental cost-effectiveness ratios (ICERs) were calculated for the base case, and a probabilistic sensitivity analysis was performed to assess the probability of cost effectiveness at different willingness-to-pay thresholds. RESULTS: The ICER for natalizumab compared with interferon-beta was 2300 pound per QALY. Compared with glatiramer acetate, it was 2000 pound per QALY, and compared with best supportive care it was 8200 pound per QALY. From a health and social care cost perspective, the ICERs were 18,700 pound, 20,400 pound and 25,500 per QALY, respectively. At a willingness-to-pay threshold of 30,000 pound per QALY, the probability of natalizumab being cost effective against any comparator from a societal perspective was >89%. CONCLUSION: If UK society is willing to pay more than 8200 pound per QALY, or Health and Social Services are willing to pay more than 26,000 pound per QALY, this analysis suggests that natalizumab is likely to be a cost-effective treatment for all patients with HARRMS.     

Cost-Effectiveness of Treating Upper Limb Spasticity Due to Stroke with Botulinum Toxin Type A: Results from the Botulinum Toxin for the Upper Limb after Stroke (BoTULS) Trial

Stroke imposes significant burdens on health services and society, and as such there is a growing need to assess the cost-effectiveness of stroke treatment to ensure maximum benefit is derived from limited resources. This study compared the cost-effectiveness of treating post-stroke upper limb spasticity with botulinum toxin type A plus an upper limb therapy programme against the therapy programme alone. Data on resource use and health outcomes were prospectively collected for 333 patients with post-stroke upper limb spasticity taking part in a randomized trial and combined to estimate the incremental cost per quality adjusted life year (QALY) gained of botulinum toxin type A plus therapy relative to therapy alone. The base case incremental cost-effectiveness ratio (ICER) of botulinum toxin type A plus therapy was £93,500 per QALY gained. The probability of botulinum toxin type A plus therapy being cost-effective at the England and Wales cost-effectiveness threshold value of £20,000 per QALY was 0.36. The point estimates of the ICER remained above £20,000 per QALY for a range of sensitivity analyses, and the probability of botulinum toxin type A plus therapy being cost-effective at the threshold value did not exceed 0.39, regardless of the assumptions made.     

Neuropsychotherapeutics in the UK: what has been the impact of NICE on prescribing?

The UK National Institute for Clinical Excellence (NICE) was set up in 1999 to advise the National Health Service (NHS) on the use of new technologies largely, but not exclusively, on the basis of their clinical and cost effectiveness. There have been problems with this, as with any developing system, most of which have arisen from issues not directly under the control of NICE. Despite this, NICE has already achieved a pivotal role in determining the uptake of new therapies into the NHS. In the area of neuropsychiatric therapies, NICE has examined a number of topics and has generally facilitated the increased use of the agents examined, approving the use, within limitations, of such drugs as riluzole, atypical antipsychotics and cholinesterase inhibitors. Although the use of some of these therapies had been growing, it had previously been restricted by funding in the NHS. As a result of NICE guidance, these funding restrictions have generally been lifted. NICE has rejected one area of neurological therapy so far--that of interferon-beta products and glatiramer acetate for multiple sclerosis--on the grounds of clinical uncertainty about long-term benefits and poor cost effectiveness. However, the UK Government has created a novel risk-sharing scheme in collaboration with the sponsoring companies to make these drugs available at a level of cost effectiveness acceptable to the NHS. The feasibility of this scheme is as yet unclear. This might be seen as either a triumph for NICE or as an undermining of it for political ends. One interesting aspect that is more prominent in neuropsychiatric disorders than in other areas of NICE activity has been the power of patient advocacy in encouraging acceptance of therapies where the evidence base was weak or the incremental cost-effectiveness ratio was unfavourable. The principles behind the activities of NICE attract wide support within the NHS, but the details of its decisions have often not been popular within NHS management who have to deliver them. Some of this relates more to the context and political environment within which NICE operates than to a failing within NICE itself. NICE will continue to become increasingly important in determining the use of new drugs within the UK NHS.     

Value based pricing,research and development,and patient access schemes. Will the United Kingdom get it right or wrong?

The National Health Service (NHS) should reward innovation it values. This will enable the NHS and the United Kingdom (UK) economy to benefit and impact positively on the Research and Development (R&D) decision making of companies. The National Institute for Health and Clinical Excellence (NICE) currently seeks to do this on behalf of the NHS. Yet the Office of Fair Trading proposals for Value Based Pricing add price setting powers – initially for the Department of Health (DH) and then for NICE. This introduces an additional substantial uncertainty that will impact on R&D and, conditional on R&D proceeding, on launch (or not) in the UK. Instead of adding to uncertainty the institutional arrangements for assessing value should seek to be predictable and science based, building on NICE''s current arrangements. The real challenge is to increase understanding of the underlying cost-effectiveness of the technology itself by collecting evidence alongside use. The 2009 Pharmaceutical Price Regulation Scheme sought to help do this with Flexible Pricing (FP) and Patient Access Schemes (PASs). The PASs to date have increased access to medicines, but no schemes proposed to date have yet helped to tackle outcomes uncertainty. The 2010 Innovation Pass can also be seen as a form of ‘coverage with evidence development.’ The NHS is understandably concerned about the costs of running such evidence collection schemes. Enabling the NHS to deliver on such schemes will impact favourably on R&D decisions. Increasing the uncertainty in the UK NHS market through government price setting will reduce incentives for R&D and for early UK launch.     

Cost-effectiveness of Ribociclib in HER2- negative breast cancer: A synthesis of current evidence

BackgroundThe main aim of this study was to investigate the cost-effectiveness of Ribociclib in the treatment of patients with breast cancer by assessing the published evidence.MethodA systematic review of the published literature was conducted to identify the economic evaluations/cost-effectiveness study of Ribociclib. In this study, several databases were inspected, including PubMed, NHS Economic Evaluation, Cochran, and Scopus. Studies were eligible if they assessed the cost-effectiveness of Ribociclib and reported incremental cost-effectiveness ratio (ICER). The study was performed and conducted following the PRISMA reporting guidelines.ResultsOf 70 studies identified, 8 articles meet our inclusion criteria. The cost-effectiveness threshold varied from $24,144.18 in Spain to $198,000/QALY in the USA. Moreover, the result demonstrated that the mean ICER varied across different countries $1,863.47/QALY in Spain and $813,132/QALY in the USA.ConclusionAmong all CDK4/6 inhibitors medications, current evidence indicated that the use of Ribociclib for HER2- negative breast cancer management was beneficial and considered to be cost-effective. Future research is needed to investigate the role of Ribociclib in long-term treatment.     

Oral antiplatelet therapy in secondary prevention of cardiovascular events: an assessment from the payer's perspective

BACKGROUND: A wide variety of oral antiplatelet trials have been carried out, and a large number of cost-effectiveness estimates based on them have been published. OBJECTIVE: To assess the cost effectiveness of oral antiplatelet treatments in the prevention of cardiovascular events. METHODS: A comprehensive literature search was carried out in PubMed and the Cochrane Library and the data reviewed. Cost-effectiveness or cost-utility studies of oral antiplatelets published since 2000 were selected. Cost-effectiveness analyses from the perspective of the UK NHS were then carried out using a Markov model with a 6-month cycle length and a lifetime horizon. Inputs from the CAPRIE, CHARISMA, (PCI)-CURE, CREDO, COMMIT, CLARITY, ESPS 2 and ESPRIT trials were included. All estimates of cost found (per event avoided, per QALY gained or per life-year gained) were included. Results were analysed in light of the National Institute for Health and Clinical Excellence (NICE) guidelines for the use of antiplatelets for the prevention of cardiovascular events and all estimates were updated to pound (year 2006 values) for easy comparison. RESULTS: Of the initial 141 studies found, 21 were included in the initial review. The literature and the Markov model subsequently used suggest that aspirin (acetylsalicylic acid) dominates placebo for the secondary prevention of cardiovascular events, as it is effective, is also less costly and is as well tolerated as placebo. Additionally, in periods or patients with elevated risk, more intensive treatment with clopidogrel (alone or together with aspirin) is cost effective compared with aspirin alone for the secondary prevention of ischaemic events. For secondary stroke prevention, combination therapy with aspirin and dipyridamole has a favourable incremental cost-effectiveness ratio (ICER) when compared with aspirin alone and, based on an indirect comparison, also when compared with clopidogrel. CONCLUSIONS: The cost-effectiveness estimates presented in this article support the NICE guidelines for the use of antiplatelets for the prevention of cardiovascular events. Based on these pharmacoeconomic data alone, aspirin should be prescribed for primary or secondary prevention among patients at high risk of cardiovascular events, dipyridamole for the secondary prevention of stroke (for a maximum of 5 years), and clopidogrel for the treatment of symptomatic cardiovascular disease or acute coronary syndrome (for a maximum of 2 years). The cost effectiveness of antiplatelets hinges on the patient's initial risk, the risk reduction associated with treatment, and the price of the treatment. Evidence suggests that the cost effectiveness of antiplatelets can be optimized by individualising the treatment decision based on patient risk and expected risk reduction.     

Eltrombopag for the treatment of chronic immune or idiopathic thrombocytopenic purpura: a NICE single technology appraisal

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of eltrombopag (GlaxoSmithKline) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of patients with chronic immune or idiopathic thrombocytopenic purpura (ITP), as part of the their Single Technology Appraisal (STA) process. The Aberdeen Technology Assessment Review (TAR) Group, commissioned to act as the evidence review group (ERG), critically reviewed and supplemented the submitted evidence. This paper describes the company submission, the ERG review and NICE's subsequent decisions. The ERG critically appraised the clinical and cost-effectiveness evidence submitted by the manufacturer, independently searched for relevant literature, conducted a critical appraisal of the submitted economic models and explored the impact of altering some of the key model assumptions as well as combining relevant sensitivity analyses. Three trials were used to inform the safety and efficacy aspects of this submission; however, one high-quality randomized controlled trial (RAISE study) was the principal source of evidence and was used to inform the economic model. Eltrombopag had greater odds of achieving the primary outcome of a platelet count between 50?×?10^?/L and 400?×?10^?/L during the 6-month treatment period than placebo (odds ratio [OR] 8.2, 99% CI 3.6, 18.7). In the eltrombopag group, 50/83 (60%) of non-splenectomized patients and 18/49 (37%) of splenectomized patients achieved this outcome. The median duration of response was 10.9 weeks for eltrombopag (splenectomized 6 and non-splenectomized 13.4) compared with 0 for placebo. Eltrombopag patients required less rescue medication and had lower odds of bleeding events for both the splenectomized and the non-splenectomized patients. For a watch-and-rescue strategy of care, the comparator was placebo and the ERG found that substantial reductions in the cost of eltrombopag are needed before the incremental cost per QALY is less than ￡30,000. There was significant uncertainty, with the incremental cost-effectiveness ratio (ICER) reported varying from ￡33,561 to ￡103,500 per QALY (splenectomized) and ￡39,657 to ￡150,245 per QALY (non-splenectomized). All costs are presented in ￡, year 2008 values, as this was the costing year for the manufacturer's model. Other than bleeding, no adverse events were modelled. In relation to the long-term treatment model, the ERG questioned the robustness of the use of non-randomized non-comparative data. The base-case results restricting the time horizon to 2 years and prescribing eltrombopag as second-line treatment post-rituximab were found to be favourable towards eltrombopag. As rituximab is not a licensed treatment for ITP, the ERG were concerned that its inclusion may not be reflective of clinical practice. None of the treatment sequences resulted in an ICER approaching the recommended threshold of ￡30,000 per QALY gained. Eltrombopag appears to be a safe treatment for ITP (although long-term follow-up studies are awaited) and has short-term efficacy. However, NICE found based on the evidence submitted and reviewed that there was no robust evidence on the long-term efficacy or cost effectiveness of eltrombopag and a lack of direct evidence for eltrombopag tested against other relevant comparators.     

Information created to evade reality (ICER): things we should not look to for answers

Cost-effectiveness analysis has been advocated in the health economics methods literature and adopted in a growing number of jurisdictions as an evidence base for decision makers charged with maximising health gains from available resources. This paper critically appraises the information generated by cost-effectiveness analysis, in particular the incremental cost-effectiveness ratio (ICER). It is shown that this ratio is used as comparative information on what are non-comparable options and hence evades the reality of the decision-maker's problem. The theoretical basis for the ICER approach is the simplification of theoretical assumptions that have no relevance to the decision maker's context. Although alternative, well established methods can be used for addressing the decision maker's problem, faced with the increasing evidence of the theoretical and empirical failures of the cost-effectiveness approach, some proponents of the approach now propose changing the research question to suit the approach as opposed to adopting a more appropriate method for the prevailing and continuing problem. As long as decision makers are concerned with making the best use of available healthcare resources, cost-effectiveness analysis and the ICER should not be where we look for answers.     

Valuing health States for use in cost-effectiveness analysis

This article reviews the general issues in valuing health states for use in cost-effectiveness analysis and the specific issues considered by the National Institute for Health and Clinical Excellence (NICE) in its recent review of the methods of technology appraisal. The general issues are how to describe health, how to value health and who should provide the values for health. The specific issues considered by NICE included whether and what should be the reference-case instrument, what to do when there are no data using the reference-case measure, what to do when the reference-case measure is not suitable and how to judge when it is not suitable, how to review and synthesize data, and how to incorporate health-state utility values into cost-effectiveness models.     

The National Institute for Health and Clinical Excellence (NICE) and drug treatment for Alzheimer's disease

Britain's National Institute for Health and Clinical Excellence (NICE) has recently issued guidance that restricts the use of cholinesterase inhibitors and memantine for the treatment of Alzheimer's disease in the National Health Service. This stance contains lessons for designers of trials, drug regulators, health economists and those developing clinical guidelines for dementia care. The debates that took place around and within NICE were about identifying the benefits of these medicines and the beneficiaries, clarifying the costs of the medication and whom bears them, the methods of weighing benefit against cost, and the consequences of using different approaches to cost-benefit analysis. This article discusses each of these themes and outlines the changes in research and clinical practice and policy making that might flow from NICE's decisions on medication use. Outcome measures that capture changes in dementia syndromes need further development. Cost-benefit analysis needs refinement with better tools than quality-adjusted life-years, and the policy implications of restricting treatments in a progressive neurodegenerative disorder need more careful consideration.     

Using QALYs in cancer: a review of the methodological limitations

The objective of this paper is to examine how well the QALY captures the health gains generated by cancer treatments, with particular focus on the methods for constructing QALYs preferred by the UK National Institute for Health and Clinical Excellence (NICE). Data were obtained using a keyword search of the MEDLINE database and a hand search of articles written by leading researchers in the subject area (with follow up of the references in these articles). Key arguments were discussed and developed at an oncology workshop in September 2009 at the Office of Health Economics. Three key issues emerged. First, the EQ-5D, NICE's preferred measure of health-related quality of life (QOL) in adults, has been found to be relatively insensitive to changes in health status of cancer patients. Second, the time trade-off, NICE's preferred technique for estimating the values of health states, involves making assumptions that are likely to be violated in end-of-life scenarios. Third, the practice of using valuations of members of the general population, as recommended by NICE, is problematic because such individuals typically display a misunderstanding of what it is really like for patients to live with cancer. Because of the way in which it is constructed, the QALY shows important limitations in terms of its ability to accurately capture the value of the health gains deemed important by cancer patients. A research agenda for addressing these limitations is proposed.